{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:50:30Z","timestamp":1787871030113,"version":"build-2784847793"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The sarcomere is the basic contractile unit of muscle fibers, bordered by Z-discs. In Drosophila, Z-disc structure and maintenance rely on actinin, and the Z-band alternatively spliced PDZ-motif protein 52 (Zasp52), a member of the Alp\/Enigma family. Zasp52 has been shown to bind actin, actinin, and itself, but its full range of functions remains unclear, as a null mutant has not been previously analyzed. To address this, we generated a CRISPR-based null mutant of Zasp52, deleting most of the \u223c50 kb locus. Null mutants are viable but flightless and display severe defects in indirect flight muscle architecture. To test redundancy, we also analyzed a double null of Zasp52 and Zasp67, the latter one being a Zasp member restricted to flight muscles. Both single and double mutants exhibit damaged myofibrils, with the double mutant showing a more severe collapse of sarcomere organization. Given the clinical importance of LIM domain-binding 3 (LDB3) mutations, the human ortholog of Zasp52, we next modeled a pathogenic variant. In humans, the P615L mutation in LDB3 has been linked to cardiomyopathy and skeletal myopathy. We engineered the orthologous substitution, Zasp52-P607L, and expressed it in Drosophila indirect flight muscles. The variant produced enlarged sarcomeres and enhanced binding, consistent with a gain-of-function disease phenotype. Together, these findings indicate that Drosophila indirect flight muscles can be used as a system to dissect Zasp function, reveal redundancy in Z-disc assembly, and provide mechanistic insight into how conserved mutations contribute to human myopathies.<\/jats:p>","DOI":"10.1093\/g3journal\/jkag148","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T16:42:12Z","timestamp":1781023332000},"source":"Crossref","is-referenced-by-count":4,"title":["Zasp52 in\n                    <i>Drosophila melanogaster<\/i>\n                    indirect flight muscles can serve as a model system to investigate the function of clinical variants causing myopathies"],"prefix":"10.1093","volume":"16","author":[{"given":"Jos\u00e9","family":"Medina-Quintana","sequence":"first","affiliation":[{"name":"Department of Biology, McGill University , Montreal, Quebec H3A 1B1 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